Project Summary Older adults are at high risk for polypharmacy particularly during transitions of care; use of potentially inappropriate medications may lead to adverse events and drug-related hospital admissions. Postoperative delirium, occurring in up to 56% of older adults undergoing surgery, is associated with longer hospital stays, increased mortality at 30 days, and reduced functional recovery. Medication regimen alterations before and after surgery prior to hospital discharge may increase postoperative delirium and influence longer-term cognition. Accurate recognition of medication-associated risk factors for postoperative delirium in the older adult surgical population is critical when defining targets for deprescribing efforts. Despite the prevalent use of potentially deliriogenic medications in the older adult surgical population, their association with postoperative delirium is poorly researched and effect on longer-term cognition unknown. The proposed research aims to investigate the impact of medications administered prior to surgery and during the in-hospital period immediately following surgery on the development of delirium and subsequent changes in cognition. This will be accomplished through the creation of robust statistical models, designed in collaboration with leading researchers in the fields of delirium and aging, controlling for established baseline predictors for postoperative delirium and the effects of all administered medications. When investigating the association between pre- and post-surgery medication use and longer-term cognition, the occurrence of intervening delirium will be accounted for given the independent effect that delirium alone may have on cognitive decline. The outcome of this work will have an immediate impact in the scientific community by informing postoperative delirium reduction efforts and deprescribing initiatives. It will also guide future research on the risk factors for both postoperative delirium and longer-term cognitive decline in the older adult surgical population. This proposed project, overseen by leading researchers at Northeastern University and Harvard Medical School, is in line with the NIA?s mission to understand and improve health among aging populations. Not only will this research help improve our understanding of the complex interplay between medications and the neurodegeneration experienced with delirium, but it will also inform future interventions designed to improve health among aging populations. All of this work will be completed through a training and mentorship plan that has been thoughtfully-developed by an interdisciplinary group of senior NIA-funded researchers that will provide an important foundation for additional independent scientific inquiry. Through their collective expertise, the sponsor team will share the skills and experience necessary to ensure the applicant excels not only in this proposed fellowship but also in his transition to a role as an independent researcher.